Mitochondrial Copy Number in Immune Cells Strongly Correlates with 15-Year Mortality
Mitochondrial copy number is a measure of the average number of mitochondrial genomes found inside each cell in a blood or tissue sample. It is to be expected that cells contain a few hundred or more mitochondria, and a similar number of circular mitochondrial genomes, at least one per mitochondrion. In the case of blood samples, only white blood cells and platelets carry mitochondria. This makes any assessment of mitochondrial function from a blood sample actually an assessment of immune function first and foremost.
A wealth of evidence suggests that mitochondrial copy number is a measure of mitochondrial function, though not necessarily a direct measure. The number of mitochondria in a cell are affected indirectly by various forms of mitochondrial dysfunction because they have consequences on mitochondrial replication, the dynamics of fusion and fission, and clearance of mitochondria by mitophagy. Mitochondrial copy number has also been shown to correlate with self-assessed health and with epigenetic age. Additionally, lower mitochondrial copy number produces what appear to be unfavorable, disease-associated epigenetic changes in a cell.
Today's open access paper adds to these past studies. The authors present interesting results from a sizable epidemiological study of older individuals with a long follow-up. There is a strong correlation between 15-year mortality and mitochondria copy number, but not a straightforward one: both high and low mitochondrial copy number do better than those in the middle tertile of the range, where there is more than a twofold increase in mortality versus the top tertile. High is best, low is worse, but being in the middle is much worse than that. This suggests a complicated relationship between mitochondrial copy number and mitochondrial function is taking place under the hood. Again, this is likely best taken as a measure of immune function first and foremost, and not necessarily indicative of what would be found for mitochondrial health in cells making up the tissues of the body. It is nonetheless food for thought, particularly given the size of the difference in mortality between groups.
The process of ageing is characterized by a progressive decline in organism functions, which leads to multimorbidity and mortality. To respond to the increase in deaths related to population ageing for the leading causes of death, ageing-related health research represents the emergent agenda. There is a battery of molecular markers of "biological age" which are explored as determinants of the rate of ageing, including the copy number of mitochondrial DNA (mtDNA-CN). Mitochondria regulate a number of cellular processes, including ATP production by oxidative phosphorylation (OXPHOS), apoptosis, β-oxidation of fatty acids and the biogenesis of iron-sulfur clusters, and are involved in the production of reactive oxygen species (ROS). Ageing is accompanied by a decay in mitochondria function, alteration in its morphology, mitochondrial content, and OXPHOS capability.
The content of mtDNA in cells and tissues is connected to metabolic activities, but how mtDNA copy number (mtDNA-CN) is adjusted to and maintained at a certain level is poorly understood. Many studies showed a reduction in mtDNA-CN in older subjects, and the estimates of an extent of decline of copies by decade have not been reported. There are facts of the association between low mtDNA-CN and all-cause and cardiovascular (CVD) mortality; however, the studies of mtDNA content in nonagenarians and centenarians have contradictory results. Referring to specific age-related outcomes, the inverse relationship between mtDNA-CN and fatal and non-fatal CVD outcomes was reported in several studies. At the same time, the estimates of potential associations between an alteration in mtDNA-CN and chronic kidney disease or cancer are rather heterogeneous depending on the cancer type and study design.
We examined a random population sample in 2003/2005 (n = 9,360, age 45-69, the HAPIEE project) and followed up for 15 years. Using a nested case-control design, we selected non-external deaths among those free from baseline cardiovascular diseases (CVD) and cancer (n = 371), and a sex- and age-stratified control (n = 785). The odds ratios (ORs) of death were 1.06 per one-decile decrease in mtDNA-CN independent of age, sex, metabolic factors, smoking, alcohol intake, and education.
The age-sex-adjusted ORs of death in the second and first tertiles of mtDNA-CN vs. the top tertile were 2.35 and 1.59; an increased risk was confined to the second tertile after controlling for smoking and metabolic factors. The multivariable-adjusted OR of CVD death was 1.92 in tertile 2 vs. the top tertile of mtDNA-CN, and for cancer-related death the ORs were 3.66 and 2.29 in tertiles 2 and 1 vs. the top tertile. In the Siberian population cohort, the mtDNA-CN was an inverse predictor of the 15-year risk of natural mortality, due to the greatest impact of CVD and cancer-related death. The findings merit attention for exploring further the role of mtDNA in human ageing and the diversity of mortality.
If my mother's mother lived to 98 and would have lived longer if not for a botched operation... then I should be all set with my mitochondria?
Or can they get modified as they get passed down?
@matt
While it is true that certain genetic factors can influence longevity, the longevity of your grandmother does not guarantee specific outcomes for your mitochondria or overall health. Mitochondria are unique cellular structures that have their own DNA, separate from the DNA found in the cell's nucleus. This mitochondrial DNA (mtDNA) is inherited maternally, which means you receive your mitochondria from your mother.
Mitochondrial DNA mutations can occur over time due to various factors, including oxidative damage and replication errors. These mutations can potentially affect mitochondrial function and may contribute to age-related diseases and conditions. While your maternal lineage may give you a baseline for certain genetic factors, it does not guarantee the absence of mitochondrial mutations or the absence of other genetic and environmental factors that can influence health and longevity.
Mitochondrial DNA mutations can accumulate over generations, and in some cases, certain mitochondrial disorders can be passed down from mother to child. These disorders can lead to various health issues and may affect energy production and cellular function.
It's important to remember that many factors contribute to an individual's health and lifespan, including genetics, lifestyle choices, environmental exposures, and access to healthcare. While having a long-lived relative is interesting and may provide some insight into genetic predispositions, it does not provide an absolute guarantee of health or lifespan.